Naturally occurring pyrrolo[2,1-c][1,4]benzodiazepines belong to a group of antitumour antibiotics derived from Streptomyces species. Recently, there is much impetus for the PBD systems as they can recognize and bind to specific sequence of DNA. Examples of naturally occurring PBDs include anthramycin, DC-81, tomaymycin, sibiromycin and neothramycin.
Pyrrolo[2,1-c][1,4]benzodiazepine antitumour antibiotics are commonly known as anthramycin class of compounds. In the last few years, a growing interest has been shown in the development of new pyrrolo[2,1-c][1,4]benzodiazepine (PBDs). These antibiotics react covalently with DNA to form an N2-guanine adduct that lies within the minor groove of duplex DNA via an acid-labile aminal bond to the electrophilic imine at the N10-C11 position (Kunimoto, S.; Masuda, T.; Kanbayashi, N.; Hamada, M.; Naganawa, H.; Miyamoto, M.; Takeuchi, T.; and Unezawa, H. J. Antibiot., 1980, 33, 665; Kohn, K. W. and Speous, C. L. J. Mol. Biol., 1970, 51, 551; Hurley, L. H.; Gairpla, C. and Zmijewski, M. Biochem. Biophys. Acta. 1977, 475, 521; Kaplan, D. J. and Hurley, L. H. Biochemistry, 1981, 20, 7572). The molecules have a right-handed twist, which allows them to follow the curvature of the minor groove of B-form double-stranded DNA spanning three base pairs. Recently, PBD-naphthalimide hybrids have been synthesized that exhibit promising in vitro anticancer activity in certain cancer cell lines and have the potential to be developed as novel anti-cancer agents. (Kamal, A.; Srinivas, O.; Ramulu, P.; Ramesh, G.; KuMar, P. P. Bioorg. Med. Chem. Lett. 2003, 13, 3577; Kamal, A.; Reddy, B. S. N.; Reddy, G. S. K.; Ramesh, G.; Bioorg. Med. Chem. Lea. 2002, 12, 1933). A recent development has been the linking of alkylamines at C-8 position of PBD through alkane spacers, which exhibit cytotoxic activity in some cancer cell lines. Moreover, these compounds with improved lyphophilicity are promising for the development of new cytotoxic agents (Kamal, A.; Laxman, N.; Ramesh, G.; Srinivas, O.; Ramulu, P.; Bioorg. Med. Chem. Lett. 2002, 12, 1919). Some examples of such PBD hybrids are illustrated in FIG. 1.

Dithiocarbamic acid esters are a common class of organic molecules. These simple molecules have shown remarkable antitumour properties, whose mode of action is thought to result from their derivatives in view of potent phase II enzyme inducers which could be used as cancer chemo preventive agents (Gerhauser, C.; You, M.; Pezzuto, J. M. Cancer Res. 1997, 57, 272; Li, R. T.; Cheng, T. M.; Cui, J. R. C. N. Patent 01118399.3, 2004. X.; Wang, R. Q.; Cui, J. R.; Li, R. T.; Cheng, T. M.; Ge, Z. M. Chin. J. Clin. Pharmacol. Ther. 2004, 9, 59).
A variety of 4-substituted-piperazine-1-carbodithioic acid 3-cyano-3,3-diphenyl-propyl esters have been synthesized and evaluated for their in vitro anticancer activity (Hou, X.; Ge, Z.; Wang, T.; Guo, W.; Cui, J.; Cheng, T.; Lai, C.; Li, R. Bioorg. Med. Chem. Lett. 2006, 16, 4214). Based on the potent anticancer activity of pyrrolo[2,1-c][1,4]benzodiazepines and dithiocarbamic acid esters the new PBD hybrids have been designed and synthesized by linking 3-cyano-3,3-diphenylpropylhexahydro-1-pyrazinecarbodithioate at C8-position of pyrrolo[2,1-c][1,4]benzodiazepine with varying alkane spacers, similarly 2-(3-hexahydro-1-pyrazinylpropyl)-2,3-dihydro-1H-benzo[de]isoquinoline-1,3-dione and 1-methylhexahydropyrazine moieties linked at C8-position of pyrrolo[2,1-c][1,4]benzodiazepine with varying dithiocarbamate side chains.